The objective of this proposal is to secure funding for a microcapillary LC-LTQ Orbitrap Elite mass spectrometer system to support shotgun proteomics-oriented, NIH-funded scientific goals of the greater Dartmouth biomedical research community. The users of the proposed system described in this application come from a broad range of departments and centers at Dartmouth College and Dartmouth Medical School, including the NCI-designated Norris Cotton Cancer Center (NCCC). Their projects represent a diverse continuum of research foci, from basic cellular mechanisms of cell cycle control and circadian rhythms to mechanisms of host-pathogen interactions and insulin signaling, to more translational projects aimed at understanding how cellular signaling is dysregulated in human lung cancers. Collectively, these research projects represent work and effort that has exceeded the capacity of the single LC-MS/MS platform that exists in all of Dartmouth for such experiments. Thus, the acquisition of a new mass spectrometer into the Dartmouth Proteomics Shared Resource is critically important to enable the completion of current, as well as future, NIH research goals of our faculty. The proposed instrumentation will be housed in our Proteomics Shared Resource, which is maintained by NCCC on behalf of the greater Dartmouth community.